乌灵菌粉贯叶连翘复方制剂干预对慢性不可预知应激大鼠模型抗抑郁作用及机制的研究

目的观察乌灵菌粉贯叶连翘复方制剂对慢性不可预知应激大鼠行为学、下丘脑-垂体-肾上腺(HPA)轴功能以及海马组织单胺类神经递质含量的影响。方法选取SD大鼠72只,随机分为正常对照组、应激模型组、氟西汀组、乌灵菌粉贯叶连翘复方制剂(高、中、低剂量)组,给药28 d,实验结束时对各组大鼠进行糖水消耗实验、Morris水迷宫实验监测,采用放免法检测血清皮质酮(CORT)、促肾上腺皮质激素(ACTH)、促肾上腺皮质激素释放激素(CRH)的浓度,高效液相-电化学法检测海马中5-羟色胺(5-HT)、去甲肾上腺素(NE)以及多巴胺(DA)的含量。结果与正常对照组相比,模型组大鼠造模4周后,糖水偏嗜度明显降低,Morris水迷宫实验中大鼠逃避潜伏期延长、在目标象限的时间及总路程减少(P0.05);血液指标显示,模型组大鼠血清中的ACTH、CORT、CRH含量明显升高,海马组织单胺神经递质5-HT、NE和DA的含量明显降低(P0.05)。与模型组相比,乌灵菌粉贯叶连翘复方制剂490 mg/kg,245 mg/kg剂量组可显著升高模型组大鼠糖水偏嗜度,缩短大鼠逃避潜伏期,增加大鼠在目标象限的时间及总路程(P0.05,P0.01)。还可显著降低模型大鼠血清中ACTH、CORT、CRH含量,升高海马组织5-HT,NE和DA的含量(P0.05)。结论乌灵菌粉贯叶连翘复方制剂具有一定的抗抑郁作用,其机制可能与增加海马组织中5-HT、DA、NE的含量,改善应激刺激导致的HPA轴功能紊乱状态有关。

Effects of mixture of Wuling powder and Hypericum perforatum L. on depressed model rats induced by chronic unpredictable stress

Objective To observe the effects of Wuling powder and Hypericum perforatum L. on changes of behavior, the hypothalamus-pituitary-adrenal (HPA) axis function, and monoamine neurotransmitters concentration of hippocampus on chronic unpredictable stress model in rats. Methods Depression model was induced by chronic unpredictable stress combining with solitary method. The stimulus lasted for 4 weeks. During the stress, the rats were intragastric given with the decoction of Wuling powder and Hypericum perforatum L. (490 mg/kg, 245 mg/kg, 123 mg/kg) and Fluoxetine hydrochloride (2.4 mg/kg) for 4 weeks. At the end of the experiment, sucrose consumption and Morris Water Maze experiment monitor the behavior of rats, such as sucrose consumption, escape latency. Moreover, the levels of the monoamine neurotransmitters in the hippocampus were analyzed by high performance liquid chromatography-electrochemistry and the content of CORT, ACTH, CRH in plasma were detected by Radioimmunoassay. Results In Morris Water Maze test, the escape latency of rats which were consecutively administrated with Wuling powder and Hypericum perforatum L. for 4 weeks decreased obviously; the total time and distance in target quadrant remarkably increased (P < 0.05). In sucrose consumption experiment, the percentage in sugar water consumption with treatment of Wuling powder and Hypericum perforatum L. increased significantly (P < 0.01). Meanwhile, the content of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in the hippocampus were significantly increased in rats of Wuling powder and Hypericum perforatum L. and the concentrations of CORT, ACTH, CRH in plasma of Wuling powder and Hypericum perforatum L. group rats were decreased obviously (P <0.05). Conclusions The disturbances of cognition, learning and memory function of rats induced by chronic unpredictable stress combining with solitary could alleviated by Wuling powder and Hypericum perforatum L., and the pharmacological effects may related to modulation of monoaminergic neurotransmitters in the hippocampus and the content of CORT, ACTH, CRH in plasma.